IL49763A - 16beta-methyl-9,11-epoxy-17alpha-hydroxy-1,4-pregnadiene-3,20-dione and its preparation - Google Patents
16beta-methyl-9,11-epoxy-17alpha-hydroxy-1,4-pregnadiene-3,20-dione and its preparationInfo
- Publication number
- IL49763A IL49763A IL49763A IL4976370A IL49763A IL 49763 A IL49763 A IL 49763A IL 49763 A IL49763 A IL 49763A IL 4976370 A IL4976370 A IL 4976370A IL 49763 A IL49763 A IL 49763A
- Authority
- IL
- Israel
- Prior art keywords
- methyl
- dione
- pregnadiene
- hydroxy
- epoxy
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0069—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C07J5/0076—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group by an alkyl group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Table Devices Or Equipment (AREA)
Abstract
1328998 Betamethasone and esters thereof I VILLAX 1 Dec 1970 [13 Dec 1969] 56961/70 Heading C2U The invention comprises (A) betamethasone 21-palmitate: and (B) a process for preparing betamethasone (I) and 21-esters thereof (Ia) from 16#-methyl-17α-hydroxypregna-1,4,9(11)- triene-3,20-dione (II) by the sequence. II#9α - bromo - 16#-methyl-11#,17α-dihydroxypregna - 1,4-diene-3,20-dione#9α,11α-epoxy-16#- methyl - 17α - hydroxypregna - 1,4 - diene - 3,20- dione # 9α - fluoro - 16# - methyl - 11#,17α- dihydroxypregna - 1,4 - diene - 3,20 - dione # 9α- fluoro - 16# - methyl - 11#,17α - dihydroxy - 21,21- diiodopregna - 1,4 - diene - 3,20 - dione # Ia # I, each step being performed under specified conditions. Specified betamethasone 21-esters are the acetate, valerate, isovalerate, palmitate, (hydrogen succinate) and (sodium succinate).
[GB1328998A]
Description
49763/2 The present invention relates to 16 £-methyl-9,ll-epoxy-17 -hydroxy-1 ,4-pregnadiene-3,20-dione of the formula: and to a process for the production of same, The above novel compound is a valuable intermediate in the synthesis of various 16 ^ -methyl corticosteroids, and especially in the process for the production of 16 ^ -methyl -9 a -fluoro-11 ^ ,17a -21-trihydroKy-l, -pregnadiene-3,'20-dione and its acylates, which is described and claimed in copending patent application No, 35823 from which the present patent application has been ftvided out.
The starting compound of the process of the present invention, namely 16^ -methyl-17-hydro>¾-l ,4,9(11 )-pregna-triene-3,20-dione of the formula: r Analysis $ CggHg^O^B = ^37.4 Calculated I Br 18.26$ Found t 18.37$ 2 ) 85.3 of the crude product obtained in the previous example is suspended in 1.011 litres methanol, 67k.3 ml chloroform is added, followed by the drop-wise addition of 200.28 ml of a normal solution of sodium hydroxide, during 25 minutes, under stirring and nitrogen atmosphere at a temperature comprised between o° and +3C. After stirring for 3 hours the reaction mixture is neutralized with 50$ aqueous acetic acid and concentrated under vacuum until a crystalline slurry is obtained. The product is then precipitated by addition of 1.390 ml of water and ice, yielding 6¾. ¾ g. of the desired new product
Claims (8)
1. 16 ^ -methyl -9,11 -epoxy-T7 a-hydroxy-l ,4-pregnadiene- 3,20-dione of the formula:
2. A process for the production of 16 ^ -methyl-9,11-epoxy-17a -hydroxy-! ,4-pregnadiene-3,20-dione which comprises reacting 16 g-methyl-17a -hydroxy-1 ,4,9(ll)-pregnatriene-3,20-dione with a bromi nation agent in the presence of aqueous perchloric acid and an inert solvent to yield 16 g-methyl-9a -bromo-Πρ ,17a -dihydroxy-1 ,4-pregnadiene-3,20-dione, and dehydrobromi nat ng this intermediate with an organic or inorganic base in an inert solvent to yield the desired 9(ll)-epoxide.
3. A process according to claim 2, wherein the brominating agent is N-bromo-succinimide or N-bromoacetamide.
4. A process according to claim 2 or 3, wherein the inert solvent is dioxane or tetrahydrofuran.
5. A process according to any of claims 1 to 4, wherein the first step is effected at a temperature of from )-15°C to +35°C.
6. A process according to any of claims 2 to 5, wherein the dehydrobromi nation is effected in an aqueous or a methanolic solution of potassium hydroxide or sodium hydroxide.
7. · A proce^ss according to any of claims 2 to 5» wherein the dehydrobromination is effected by sodium methoxide in an inert solvent*
8. A process for the production of the 9(ll )-epoxides defined in claim 1, substantially as hereinbefore described and with reference to the example.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PT5292369 | 1969-12-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL49763A true IL49763A (en) | 1977-08-31 |
Family
ID=20081704
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL49763A IL49763A (en) | 1969-12-13 | 1970-12-10 | 16beta-methyl-9,11-epoxy-17alpha-hydroxy-1,4-pregnadiene-3,20-dione and its preparation |
| IL35823A IL35823A (en) | 1969-12-13 | 1970-12-10 | Process for the preparation of 16beta-methyl-9alpha-fluoro-11beta,17alpha,21-trihydroxy-1,4-pregnadiene-3,20-dione and its 21-acylates |
| IL49763A IL49763A0 (en) | 1969-12-13 | 1976-06-10 | Novel 9,11-epoxy-pregnadienes and their preparation |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL35823A IL35823A (en) | 1969-12-13 | 1970-12-10 | Process for the preparation of 16beta-methyl-9alpha-fluoro-11beta,17alpha,21-trihydroxy-1,4-pregnadiene-3,20-dione and its 21-acylates |
| IL49763A IL49763A0 (en) | 1969-12-13 | 1976-06-10 | Novel 9,11-epoxy-pregnadienes and their preparation |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3792046A (en) |
| JP (3) | JPS508080B1 (en) |
| AT (1) | AT304774B (en) |
| BE (1) | BE760236A (en) |
| CA (1) | CA932321A (en) |
| CH (1) | CH551395A (en) |
| DE (1) | DE2059050A1 (en) |
| DK (1) | DK130991B (en) |
| ES (1) | ES386385A1 (en) |
| FR (1) | FR2081356B1 (en) |
| GB (1) | GB1328998A (en) |
| IL (3) | IL49763A (en) |
| NL (1) | NL166694C (en) |
| NO (1) | NO136049C (en) |
| ZA (1) | ZA708393B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58212359A (en) * | 1982-05-25 | 1983-12-10 | マグネツト・モ−トル・ゲゼルシヤフト・フユア・マグネツトモ−トリツシエ・テクニ−ク・ミツト・ベシユレンクテル・ハフツンク | Rotary electric machine |
| JPS6261175U (en) * | 1985-10-02 | 1987-04-16 | ||
| JPS62135570U (en) * | 1986-02-19 | 1987-08-26 | ||
| JP2004536088A (en) * | 2001-06-18 | 2004-12-02 | ファルマシア・アンド・アップジョン・カンパニー | Production method of 11β, 17α, 21-trihydroxy-6α-methylpregna-1,4-diene-3,20-dione 21-acetate |
| US20040006240A1 (en) * | 2001-06-18 | 2004-01-08 | Pearlman Bruce Allen | Process to prepare 11beta,17alpha ,21-trihydroxy-6alpha-methylpregna-1,4-diene-3,20-dione 21-acetate |
| CN101555268B (en) * | 2009-05-21 | 2011-11-30 | 广西万德药业股份有限公司 | Preparation method for glucocorticoid 9, 11 epoxy intermediate product |
| CN102304163A (en) * | 2011-07-11 | 2012-01-04 | 浙江仙居仙乐药业有限公司 | Fluorous synthesis method of betamethasone |
| CN104945464B (en) * | 2015-04-17 | 2016-10-26 | 浙江仙居仙乐药业有限公司 | A kind of synthetic method of betamethasone epoxy hydrolysate |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1274397A (en) * | 1958-12-16 | 1961-10-27 | Chimiotherapie Lab Franc | Process for the preparation of 9alpha-fluoro 16alpha-methyl delta1, 4-pregnadienes derivatives |
| FR1243528A (en) * | 1959-08-05 | 1960-10-14 | Chimiotherapie Lab Franc | Process for the acetoxylation of steroids in 21 via diiodinated derivatives |
-
1970
- 1970-12-01 DE DE19702059050 patent/DE2059050A1/en not_active Ceased
- 1970-12-01 GB GB5696170A patent/GB1328998A/en not_active Expired
- 1970-12-02 DK DK613670AA patent/DK130991B/en unknown
- 1970-12-08 NL NL7017904.A patent/NL166694C/en not_active IP Right Cessation
- 1970-12-08 CA CA100128A patent/CA932321A/en not_active Expired
- 1970-12-10 CH CH1828270A patent/CH551395A/en not_active IP Right Cessation
- 1970-12-10 IL IL49763A patent/IL49763A/en unknown
- 1970-12-10 IL IL35823A patent/IL35823A/en unknown
- 1970-12-11 NO NO4780/70A patent/NO136049C/en unknown
- 1970-12-11 AT AT1119470A patent/AT304774B/en active
- 1970-12-11 FR FR7044641A patent/FR2081356B1/fr not_active Expired
- 1970-12-11 BE BE760236A patent/BE760236A/en unknown
- 1970-12-11 ZA ZA708393A patent/ZA708393B/en unknown
- 1970-12-11 JP JP45109617A patent/JPS508080B1/ja active Pending
- 1970-12-12 ES ES386385A patent/ES386385A1/en not_active Expired
-
1972
- 1972-08-07 US US00278394A patent/US3792046A/en not_active Expired - Lifetime
-
1976
- 1976-06-10 IL IL49763A patent/IL49763A0/en unknown
-
1978
- 1978-11-08 JP JP13683678A patent/JPS5721280B1/ja active Pending
- 1978-11-08 JP JP13683778A patent/JPS5721279B1/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL35823A (en) | 1977-08-31 |
| ZA708393B (en) | 1972-07-26 |
| DK130991C (en) | 1975-12-08 |
| CH551395A (en) | 1974-07-15 |
| IL35823A0 (en) | 1971-02-25 |
| BE760236A (en) | 1971-05-17 |
| FR2081356A1 (en) | 1971-12-03 |
| NO136049B (en) | 1977-04-04 |
| FR2081356B1 (en) | 1976-09-17 |
| DE2059050A1 (en) | 1972-04-06 |
| GB1328998A (en) | 1973-09-05 |
| US3792046A (en) | 1974-02-12 |
| IL49763A0 (en) | 1976-08-31 |
| NL7017904A (en) | 1971-06-15 |
| AT304774B (en) | 1973-01-25 |
| NL166694B (en) | 1981-04-15 |
| JPS5721279B1 (en) | 1982-05-06 |
| NL166694C (en) | 1981-09-15 |
| ES386385A1 (en) | 1973-03-16 |
| NO136049C (en) | 1977-07-13 |
| JPS508080B1 (en) | 1975-04-01 |
| DK130991B (en) | 1975-05-12 |
| JPS5721280B1 (en) | 1982-05-06 |
| CA932321A (en) | 1973-08-21 |
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